Cardiogenic reflexes after immune injury of the heart

Afferent and efferent spike activity from the parasympathetic (vagus) and sympathetic cardiac nerves were recorded simultaneously with ECG, and indices of heart function were measured in acute experiments on anesthetized dogs, which allowed us to study the modifications of cardio-cardiac reflex influences after a local immune heart injury. After an injury nidus has been formed in the heart, cardiogenic depressor reflexes evoked by an intracoronary application of veratrine or bradykinin were considerably suppressed or even abolished, and afferent spike activity in the vagus cardiac nerves noticeably decreased. At the same time, both the facilitation of activity in sympathetic afferent fibers and pressor reflex effects were preserved after the heart injury. Different localization of vagus and sympathetic afferent structures in the heart and their specialized sensitivity to the biologically active substances are suggested as the factors determining the pattern of cardiogenic reflex influences after a heart injury.Neirofiziologiya/Neurophysiology, Vol. 27, No. 1, pp. 18–25, January–February, 1995.     

Effects of phosphocreatine on the heart nerve structures under conditions of local immune impairment (electrophysiological and neurochemical aspects)

Effects of phosphocreatine on the neurohumoral mechanisms controlling the heart under conditions of a local immune injury were studied in acute experiments on anesthetized dogs using electrophysiological, biochemical, and electron microscopy techniques. After the development of heart injury, cardiogenic depressor reflexes evoked by an intracoronary injection of veratrine and mediated by vagus mechanisms disappeared, while pressor reflexes became dominating. This phenomenon correlated with an increase in concentration of a vasoconstrictor agent, leucotriene LTC₄, in the blood and with a considerable ultrastructural impairment of nerve terminals in the myocardium. Preliminary injection of phosphocreatine prevented the development of structural impairments, favored the preservation of vagosympathetic depressor reflex, and not only prevented the increase in LTC₄ concentration, but even dramatically decreased its level (by 82%, as compared with the initial level). We concluded that complex protective effect of phosphocreatine provides structural and functional preservation of the receptor apparatus in the heart and can play a considerable role in normalization of neurohumoral mechanisms controlling the heart under conditions of pathological impairment.Neirofiziologiya/Neurophysiology, Vol. 27, No. 2, pp. 140–146, March–April, 1995.     

Effect of indomethacin-induced inhibition of arachidonic acid metabolism on the development of cardiogenic reflexes

In acute experiments on anesthetized cats, afferent spike activity from the parasympathetic (vagal) and sympathetic cardiac nerves, ECG, and cardiodynamic indices were recorded. The effects of indomethacin-induced blockade of cyclo-oxygenase pathway in metabolism of arachidonic acid on the development of cardiogenic reflex responses after intracoronary injections of veratrine, bradykinin, or prostacyclin were tested. It was found that after indomethacin injection depressor cardiogenic vagal reflexes, evoked by veratrine or bradykinin administrations, became significantly suppressed or practically disappeared. This was accompanied by a drop in the frequency of afferent vagal activity in the cardiac nerves. This effect could be observed throughout the entire period of influence of indomethacin (about 2 h after its injection). Veratrine or bradykinin, being injected simultaneously with prostacyclin, provided faster partial recovery of depressor responses (at 1 h) and promoted some activation of vagal cardiac nerves, despite the effect of indomethacin. Injection of indomethacin did not change the pattern of sympathetic afferent activity. It is suggested that the main derivative of cyclo-oxygenase pathway of arachidonic acid metabolism, prostacyclin, is able to modulate vagal nervous activity at the level of afferent structures in the heart. Prostacyclin may appear a humoral component of cardiogenic depressor reflexes of a vagal nature.Neirofiziologiya/Neurophysiology, Vol. 28, No. 1, pp. 53–61, January–February, 1996.     

Spinal GABA(A) receptors do not mediate the sympathetic baroreceptor reflex in the rat

Activation of baroreceptors causes efferent sympathetic nerve activity (SNA) to fall. Two mechanisms could account for this sympathoinhibition: disfacilitation of sympathetic preganglionic neurons (SPN) and/or direct inhibition of SPN. The roles that spinal GABA and glycine receptors play in the baroreceptor reflex were examined in anesthetized, paralyzed, and artificially ventilated rats. Spinal GABA(A) receptors were blocked by an intrathecal injection of bicuculline methiodide, whereas glycine receptors were blocked with strychnine. Baroreceptors were activated by stimulation of the aortic depressor nerve (ADN), and a somatosympathetic reflex was used as control. After an intrathecal injection of vehicle, there was no effect on any measured variable or evoked reflex. In contrast, bicuculline caused a dose-dependent increase in arterial pressure, SNA, phrenic nerve discharge, and it significantly facilitated the somatosympathetic reflex. However, bicuculline did not attenuate either the depressor response or sympathoinhibition evoked after ADN stimulation. Similarly, strychnine did not affect the baroreceptor-induced depressor response. Thus GABA(A) and glycine receptors in the spinal cord have no significant role in baroreceptor-mediated sympathoinhibition.     

Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid

Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.     

Role of Acetylcholine in the Modulation of Activity of Neocortical Neurons in Awake Animals Performing an Instrumental Conditioned Reflex

We studied modulatory effects of the cholinergic system on the activity of sensorimotor cortex neurons related to realization of an instrumental conditioned placing reflex. Experiments were carried out on awake cats; multibarrel glass microelectrodes were used for extracellular recording of impulse activity of neurons in the sensorimotor cortex and iontophoretic application of synaptically active agents within the recording region. The background and reflex-related activity was recorded in the course of realization of conditioned movements, and then changes of spiking induced by applications of the testing substances were examined. Applications of acetylcholine and carbachol resulted in increases in the intensity of impulse reactions of neocortical neurons evoked by presentation of an acoustic signal and in simultaneous shortening of the response latencies. An agonist of muscarinic receptors, pylocarpine, exerted a similar effect on the evoked activity of sensorimotor cortex neurons. Blockers of muscarinic receptors, atropine and scopolamine, vice versa, sharply suppressed impulse reactions of cortical neurons to afferent stimulation and simultaneously increased latencies of these responses. Applications of an agonist of nicotinic receptors, nicotine, was accompanied by suppression of impulse neuronal responses, an increase in the latency of spike reactions to presentation of a sound signal, and a corresponding increase in the latency of a conditioned motor reaction. In contrast, application of an antagonist of nicotinic receptors, tubocurarine, significantly intensified neuronal spike responses and shortened their latency. The mechanisms underlying the effects of antagonists of membrane muscarinic and nicotinic cholinoreceptors and the role of activation of these receptors in the modulation of activity of pyramidal and non-pyramidal neocortical neurons related to realization of the instrumental motor reflex are discussed.     

Organization of Efferent Sympathetic Influences Related to Cardiogenic Depressor Reflexes

In acute experiments on anesthetized dogs under open chest conditions, we studied characteristics of the efferent sympathetic influences on the heart and vessels related to realization of cardiogenic depressor vagus-mediated reflexes. Catheterization of the heart cavities and parallel recording of the mass efferent spike activities in the cardiac and vertebral sympathetic nerves and of the pressure in the aortic ventricle of the heart were used. We found that reflex shifts in the spike activity in the cardiac and vertebral nerves elicited by pharmacological stimulation of the left heart (intracoronary injections of veratrine or adrenaline) and by its nidal immune impairment resulting from injection of a cytotoxic serum demonstrate similar direction (a drop in the frequency of the efferent sympathetic activity). Yet, the dynamics of such inhibitory responses to the influence of the same stimulus and their intensity in one nerve or another and those in one and the same nerve under the influence of different stimuli are considerably dissimilar. Thus, realization of vagus-mediated cardiogenic reflexes is characterized by clear heterogeneity of the efferent sympathetic control of different regions of the cardiovascular system. Such a specificity can provide differential regulation of the heart function and functions of the vascular bed related to different cardiogenic influences (both in the norm and under conditions of formation of an injury nidus in the heart).     

Depressor reactions to sural nerve stimulation in intact unanesthetized cats]

Changes in the arterial pressure, in the heart and respiratory rate evoked by the gastrocnemuis nerve stimulation were studied on conscious cats before and during intravenous injection of noradrenaline. Stimulation of the gastrocnemius nerve increased the arterial pressure, the heart and respiratory rates. The same stimulation of the nerve during hypertension caused by noradrenaline injection led to the fall of arterial pressure and tachycardia. The depressor response failed to change under the effect of the beta-adrenoreceptor block and disappeared after the m-cholinoreceptor block with methylatropine. The depressor response was absent in the unanesthetized decerebrated cats. It is supposed that the depressor response of the arterial pressure depended on the strong cholinergic vasodilatation, reflexively evoked by stimulation of the motor nerve in the intact cats.     

Biocybernetic studies on reflectory heart modification in the rabbit]

In rabbits the depressor nerves and cardiac vagal branches were stimulated. Their actions on heart rate, atrio-ventricular conduction time, myocardial action potential and mean central blood pressure were recorded. The frequency-effect characteristics of the chronotropic, dromotropic and electrotropic actions on the heart, resulting from afferent and efferent nerve stimulation, are compared. The participation of each of the depressor nerves in their total effects on heart rate and blood pressure is studied. Time courses of heart rate and blood pressure decrease by afferent and efferent nerve stimulation with sinusoidally modulated pulse rates are presented. The results are discussed with respect to the different dynamics of blood pressure and heart rate control. It is concluded that at least two mechanisms are involved in blood pressure control by the depressor nerves: 1. Decrease of vascular resistance by lowering the sympathetic tone. 2. Decrease of heart rate by enhancing the cardiac vagal activity. It is suggested that the parasympathetic control unit compensates rapid disturbances, whereas the slow-acting sympathetic vascular mechanism exerts a long-time pressure control of high efficiency.     

Oxidative stress impairs cardiac chemoreflexes in diabetic rats

We investigated the effects of diabetes mellitus and antioxidant treatment on the sensory and reflex function of cardiac chemosensory nerves in rats. Diabetes was induced by streptozotocin (STZ; 85 mg/kg ip). Subgroups of sham- and STZ-treated rats were chronically treated with an antioxidant, vitamin E (60 mg/kg per os daily, started 2 days before STZ). Animals were studied 6-8 wk after STZ injection. We measured renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MABP), and cardiac vagal and sympathetic afferent activities in response to stimulation of chemosensitive sensory nerves in the heart by epicardial application of capsaicin (Caps) and bradykinin (BK). In cardiac sympathetic-denervated rats, Caps and BK (1-10.0 microg) evoked a vagal afferent mediated reflex depression of RSNA and MABP, which was significantly blunted in STZ-treated rats (P < 0.05). In vagal-denervated rats, Caps and BK (1-10.0 microg) evoked a sympathetic afferent-mediated reflex elevation of RSNA and MABP, which also was significantly blunted in STZ-treated rats (P < 0.05). Chronic vitamin E treatment effectively prevented these cardiac chemoreflex defects in STZ-treated rats without altering resting blood glucose or hemodynamics. STZ-treated rats with insulin replacement did not exhibit impaired cardiac chemoreflexes. In afferent studies, Caps and BK (0.1 g-10.0 microg) increased cardiac vagal and sympathetic afferent nerve activity in a dose-dependent manner in sham-treated rats. These responses were significantly blunted in STZ-treated rats. Vitamin E prevented the impairment of afferent discharge to chemical stimulation in STZ rats. The following were concluded: STZ-induced, insulin-dependent diabetes in rats extensively impairs the sensory and reflex properties of cardiac chemosensitive nerve endings, and these disturbances can be prevented by chronic treatment with vitamin E. These results suggest that oxidative stress plays an important role in the neuropathy of this autonomic reflex in diabetes.     

Study of tonic and evoked electrical activity in efferent fibers of the sympathetic nerve in white rats

In anaesthetised Wistar rats, electrical sympathetic activity and a somatosympathetic reflex in the cervical sympathetic trunk elicited by a single electrical shock to forelimb or hindlimb afferent nerves, were recorded. The spontaneous activity was shown to conform with the pulse and respiratory waves of arterial pressure. Somatosympathetic reflex consists of early and late discharges evoked by somatic myelinated afferent fibres stimulation, and C-response elicited by stimulation of unmyelinated afferent fibres in spinal nerves.     

Baroreceptor afferent discharge in the pregnant rat

Pregnancy is associated with blunted reflex responses to cardiac and arterial baroreceptor stimulation. We tested the hypothesis that arterial baroreceptor afferent discharge is attenuated in response to a pressure stimulus in pregnant rats. Multifiber aortic depressor nerve activity (ADNA), mean arterial pressure (MAP), and heart rate were measured in anesthetized (pentobarbital sodium, 35 mg/kg ip) late-pregnant and virgin rats in response to increases ?phenylephrine (PE), 1.5-24 microg. kg(-1). min(-1) and 1-16 microg/kg and decreases ?sodium nitroprusside (SNP), 5-80 microg. kg(-1). min(-1) and 0.05-16 microg/kg in MAP. Resting MAP was lower in pregnant rats, but changes in MAP were similar to those in virgin rats during both PE and SNP administration. ADNA was significantly attenuated in pregnant animals during both PE and SNP infusions (P < 0.05) due to a more rapid adaptation to the pressure stimulus. Bolus drug administration evoked similar changes in MAP and ADNA in both groups; however, the maximum decrease in ADNA was achieved at the lowest dose of SNP in pregnant rats. Thus baroreceptor afferent discharge is attenuated in pregnant rats, and this involves a more rapid adaptation to a pressure stimulus.     

The Gigantocellular Depressor Area Revisited

1. In studies conducted with Dr Donald Reis we described a functionally distinct region of the rat medullary reticular formation that we called the Gigantocellular Depressor Area (GiDA). The GiDA was defined as a region from which vasodepressor and sympathoinhibitory responses were evoked by nanoinjections of glutamate. We later showed that cells in the GiDA project to autonomic nuclei in the medulla, brainstem, and spinal cord, including the intermediolateral cell column. We also showed that kainic acid lesions of the GiDA induce hypertension and block the baroreceptor reflex evoked by electrical stimulation of the aortic depressor nerve. The present studies describe the effects of muscimol nanoinjections into the GiDA.2. Nanoinjections of muscimol were made in the GiDA of anesthetized rats and changes in arterial pressure, heart rate, and responses to aortic depressor nerve stimulation were measured.3. Bilateral nanoinjections of muscimol into the GiDA evoke an increase in arterial pressure and lead to fulminating hypertension. Unilateral injections of muscimol into the GiDA block the baroreflex response evoked by electrical stimulation of the ipsilateral aortic depressor nerve. However, these unilateral injections of muscimol into the GiDA evoked profound falls in arterial pressure to nearly spinal levels. In spite of this fall in blood pressure, heart rate also decreased significantly and there was not a compensatory tachycardia. Both the arterial pressure and baroreceptor responses required several hours to recover following the muscimol injections.4. Although these data are consistent with the proposal that the GiDA is critical for the baroreflex, the opposing effects on blood pressure of unilateral and bilateral injections of muscimol are difficult to reconcile with our current models of central sympathetic regulation.     

Nitric oxide modulates local reflexes of the tailfan of the crayfish

Electrical stimulation of sensory neurons that innervate receptors on the tailfan of crayfish evokes a reflex response of motor neurons that produce movements of the blades of the tailfan, the uropods. We analyzed the modulatory effects of nitric oxide (NO) on the spike frequency of the reflex response. Bath application of L-arginine and SNAP, which elevate endogenous and exogenous NO levels, increased the frequency of the evoked response, whereas the application of L-NAME and PTIO, which reduce NO levels, decreased the frequency of the response. To determine through what pathway and target NO exerted these effects we bath applied ODQ, an inhibitor of soluble guanylyl cyclase (sGC), which decreased the frequency of response, and 8-br-cGMP, which increased the spike frequency of response. To provide further evidence that NO acts via sGC, we elevated NO levels with L-arginine while simultaneously inhibiting sGC with ODQ. This application reduced the response to control levels, indicating that NO in the terminal ganglion of crayfish acts via sGC to modulate cGMP levels, which in turn regulate the responses of the uropod motor neurons.     

Radular mechanosensory neuron in the buccal ganglia of the terrestrial slug,Incilaria fruhstorferi

A radular mechanosensory neuron, RM, was identified in the buccal ganglia of Incilaria fruhstorferi. Fine neurites ramified bilaterally in the buccal ganglia, and main neurites entered the subradular epithelium via buccal nerve 3 (n3). When the radula was distorted by bending, RM produced an afferent spike which was preceded by an axonic spike recorded at n3. The response of RM to radular distortion was observed even in the absence of Ca²⁺, which drastically suppressed chemical synaptic interactions. Therefore, RM was concluded to be a primary radular mechanoreceptor.During rhythmic buccal motor activity induced by food or electrical stimulation of the cerebrobuccal connective, RM received excitatory input during the radular retraction phase. In the isolated buccal ganglia connected to the radula via n3s, the afferent spike, which had been evoked by electrical stimulation of the subradular epithelium, was broadened with the phasic excitatory input. Since the afferent spike was also broadened by current injection into the soma, depolarization due to the phasic input may have produced the spike broadening.Spike broadening was also observed during repetitive firing evoked by current injection. The amplitude of the excitatory postsynaptic potential in a follower neuron increased depending on the spike broadening of RM.Abbreviations CBC cerebrobuccal connective - EPSP excitatory postsynaptic potential - n1,n3 buccal nerves 1 and 3 - RBMA rhythmic buccal motor activity - RM radular mechanosensory neuron - SMT supramedian radular tensor neuron     

Physiological characterization of antennular flicking reflexes in the crayfish

The cellular substrates of antennular flicking behavior in the crayfish Procambarus clarkii were investigated. Flicking involves fast downward movements of the external filament of each biramous antennule (1st antenna), and is mediated by phasic contractions of a short muscle, the external filament depressor. Phasic contractions of the external filament depressor depend upon stereotyped impulse bursts in a single motorneuron (P1). These bursts have a characteristic impulse frequency profile that is consistent upon successive occurrences. The temporal characteristics of the impulse burst suggest that the central depolarizations generating each burst may be similar to driver potentials described for motor neurons in crustacean cardiac ganglia. Responses of the external filament to odorants have a long latency and are characterized by repetitive bursts and tonic activity in some external filament depressor fibers. Tonic activity in a slowly contracting muscle, the antennular depressor muscle, is also evoked by chemical stimulation. Flicking is consistently evoked only by mechanical or hydrodynamic stimulation of the cephalothorax, antennae and antennules. The sensitivity and short latency of the hydrodynamic antennule-generated flick reflex is consistent with the sensitivity of rapidly conducting, hydrodynamically activated mechanoreceptor neurons in both antennular filaments. I propose that antennular flicking, which has been shown to enhance the dynamic response characteristics of olfactory receptor neurons on the external antennular filament, has evolved as a response to the turbulence associated with fluid movement, within which chaotic odorant concentration fronts may be imbedded. Accepted: 23 October 1996     

Are prostaglandins involved in atrial natriuretic peptide mechanisms of cardiovascular control?

Atrial natriuretic peptide (ANP) can excite cardiac nerve endings and invoke a decrease in arterial blood pressure and a reduction in renal sympathetic nerve activity. Our laboratory has previously demonstrated that this renal depressor reflex was invoked by systemic injection of ANP and not by the direct application of ANP to the epicardium, a major locus for vagal afferents. We now examine whether inhibition of prostaglandin synthesis impairs reflex responses that are normally associated with ANP injections. Renal sympathetic nerve activity, arterial blood pressure, and heart rate were recorded in anesthetized rats. Indomethacin was used to inhibit prostaglandin synthesis through the cyclooxygenase pathway. The ANP-mediated decrease in arterial blood pressure and renal sympathetic nerve activity, observed when prostaglandin synthesis was inhibited, did not differ significantly from the decreases observed in these parameters when prostaglandin synthesis was not inhibited. Heart rate remained unchanged. Our results suggest that the sympatho-inhibitory effects of ANP do not require prostaglandins as intermediary compounds.     

Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and perifornical area

Neurons within the dorsomedial hypothalamic nucleus (DMH) and perifornical area (PeF), which lie within the classic hypothalamic defense area, subserve the cardiovascular response to psychological stress. Previous studies have shown that electrical stimulation of the hypothalamic defense area causes inhibition of the cardiac and (in some cases) sympathetic components of the baroreceptor reflex. In contrast, naturally evoked psychological stress does not appear to be associated with such inhibition. In this study, we tested the effect of specific activation of neurons within the DMH and PeF on the baroreflex control of renal sympathetic nerve activity and heart rate in urethane-anesthetized rats. Microinjection of bicuculline (a GABA(A) receptor antagonist) into the DMH caused dose-dependent increases in heart rate and renal sympathetic activity, shifted the baroreflex control of both variables to higher levels (i.e., increased the upper and lower plateaus of the baroreflex function curves, and increased the threshold, midpoint, and saturation levels of mean arterial pressure). The maximum gain of the sympathetic component of the baroreflex was also increased, while that of the cardiac component was not significantly changed. Increases in the midpoint were very similar in magnitude to the evoked increases in baseline mean arterial pressure. Microinjection of bicuculline into the PeF evoked very similar effects. The results indicate that disinhibition of neurons in the DMH/PeF region not only increases sympathetic vasomotor activity and heart rate but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure.     

AT1 receptors in the nucleus tractus solitarii mediate the interaction between the baroreflex and the cardiac sympathetic afferent reflex in anesthetized rats

The cardiac "sympathetic afferent" reflex (CSAR) has been reported to increase sympathetic outflow and depress baroreflex function via a central angiotensin II (ANG II) mechanism. In the present study, we examined the role of ANG II type 1 (AT(1)) receptors in the nucleus tractus solitarii (NTS) in mediating the interaction between the CSAR and the baroreflex in anesthetized rats. We examined the effects of bilateral microinjection of AT(1) receptor antagonist losartan (100 pmol) into the NTS on baroreflex control of renal sympathetic nerve activity (RSNA) before and after CSAR activation by epicardial application of capsaicin (0.4 microg). Using single-unit extracellular recording, we further examined the effects of CSAR activation on the barosensitivity of barosensitive NTS neurons and the effects of intravenous losartan (2 mg/kg) on CSAR-induced changes in activity of NTS barosensitive neurons. Bilateral NTS microinjection of losartan significantly attenuated the increases in arterial pressure, heart rate, and RSNA evoked by capsaicin but also markedly (P < 0.01) reversed the CSAR-induced blunted baroreflex control of RSNA (Gain(max) from 1.65 +/- 0.10 to 2.22 +/- 0.11%/mmHg). In 17 of 24 (70.8%) NTS barosensitive neurons, CSAR activation significantly (P < 0.01) inhibited the baseline neuronal activity and attenuated the neuronal barosensitivity. In 11 NTS barosensitive neurons, intravenous losartan effectively (P < 0.01) normalized the decreased neuronal barosensitivity induced by CSAR activation. In conclusion, blockade of NTS AT(1) receptors improved the blunted baroreflex during CSAR activation, suggesting that the NTS plays an important role in processing the interaction between the baroreflex and the CSAR via an AT(1) receptor-dependent mechanism.     

Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs

Baroreceptor afferent fibers synapse in the nucleus tractus solitarius (NTS) of the medulla. Neuronal cannabinoid (CB)(1) receptors are expressed in the NTS and central administration of CB(1) receptor agonists affect blood pressure (BP) and heart rate. In addition, there is evidence that endocannabinoids are produced in the brain stem. This study examined whether changes in CB(1) receptor activity in the NTS modulated the baroreceptor reflex, contributing to changes seen in BP and heart rate. Baroreflexes were evoked in anesthetized dogs by pressure ramp stimulations of the isolated carotid sinus before and after microinjection of CB(1) receptor agonist WIN-55212-2 (1.25-1.50 pmol) or antagonist SR-141716 (2.5-3.0 pmol) into cardiovascular regions of the NTS. Microinjection of the SR-141716 did not affect baseline BP or baroreflex sensitivity. However, SR-141716 significantly prolonged the time needed to return to the baseline level of BP after the pressure ramp. Microinjection of WIN-55212-2 had no effect on the baroreflex. These data suggest that endocannabinoids can modulate the excitability of NTS neurons involved in the baroreceptor reflex, leading to modulation of baroreflex regulation.